Chemistry - A European Journal
Chemistry - A European Journal
4 years ago

Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity

Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity
Jeanne Crassous, Thibault E. Schmid, Prasad L. Polavarapu, Marie S. T. Morin, Charlie Blons, Marc Mauduit, Stéphanie Halbert, Sophie Colombel-Rouen, Craig M. Williams, Paul V. Bernhardt, Hélène Gérard, Thibault Reynaldo, Olivier Baslé, Cody L. Covington, Christophe Crévisy, Sean N. Cuskelly, Thomas Vives
The first stereocontrolled Cu-catalyzed sequential 1,6/1,4-asymmetric conjugate addition (ACA) of C-metalated hard nucleophiles to cyclic dienones is reported. The use of DiPPAM (diphenylphosphinoazomethinylate) followed by a phosphoramidite as the stereoinducing ligands facilitated both high ee values for the 1,6-ACA and high de values for the 1,4-ACA reaction components, which thus gave enantioenriched 1,3-dialkylated moieties. The absolute configurations were determined by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X-ray analysis. Interestingly, DFT calculations for the mechanism of enantioselective 1,6-addition by using an unprecedented Cu–Zn bimetallic catalytic system confirmed this attribution. Lastly, exploring intramolecular cyclization avenues for enantioenriched 1,3-dialkylated products provided access to the challenging drimane skeleton. Taking control: A stereocontrolled Cu-catalyzed sequential 1,6/1,4-asymmetric conjugate addition (ACA; see scheme) of C-metalated hard nucleophiles to cyclic dienones is reported. High ee and de values were reached to give enantioenriched 1,3-dialkylated moieties. The absolute configurations were determined by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X-ray analysis.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201606034

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